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Constitutive overexpression of the L-selectin gene in fresh leukemic cells
of adult T-cell leukemia that can be transactivated by human T- cell
lymphotropic virus type 1 Tax
M Tatewaki, K Yamaguchi, M Matsuoka, T Ishii, M Miyasaka, S Mori, K Takatsuki and T Watanabe
Department of Pathology, University of Tokyo, Japan.
L-selectin is an adhesion molecule of the selectin family that mediates the
initial step of leukocyte adhesion to vascular endothelium. Upon cellular
activation, expression of the L-selectin gene is downregulated at both the
protein and mRNA levels. To understand the mechanism of leukemic cell
infiltration into organs, we studied the expression and regulation of
L-selectin mRNA in fresh leukemic cells of adult T-cell leukemia (ATL)
patients and investigated the response of the L-selectin promoter to human
T-cell lymphotropic virus type 1 (HTLV-1) Tax, which is a viral
transcriptional transactivator. Flow cytometry showed that L- selectin was
expressed on fresh ATL cells along with other activation antigens. Northern
blot analysis showed that ATL cells overexpressed that L-selectin mRNA and
that the level was aberrantly upregulated after PMA stimulation. Studies
using in situ hybridization showed expression of the L-selectin mRNA in the
infiltrating leukemic cells in the liver of two ATL patients. Intravenous
injection of a rat T-cell line that overexpresses L-selectin showed
increased organ infiltration. The induction of Tax expression in JPX9 cells
resulted in about a twofold increase in the mRNA expression levels compared
with the basal level. Chloramphenicol acetyltransferase (CAT) assay after
transient cotransfection showed about a fivefold transactivation of the L-
selectin promoter by Tax. The serum level of the shed form of L- selectin
was significantly increased in ATL patients (mean +/- SD, 4,215.4 +/- 4,111
ng/mL) compared with those of asymptomatic carriers and healthy blood
donors (mean +/- SD, 1,148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL,
respectively). These results indicated that ATL cells constitutively
overexpress the L-selectin gene that can be transactivated by HTLV-1 Tax.
The overexpression of L-selectin, as well as of inflammatory cytokines, by
ATL cells may provide a basis for ATL cells to attach the vascular
endothelium, leading to transmigration and organ infitration.
Volume 86,
Issue 8,
pp. 3109-3117,
10/15/1995
Copyright © 1995 by The American Society of Hematology
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